Efficient exploration of conformational space using the stochastic search method: Application to beta-peptide oligomers

An efficient and general strategy for the determination of all low-energy m inima of a molecule, viz., the stochastic conformational jump procedure, ha s been implemented in the BOSS package. In this method, a new structure is generated by random movement ("kick") of individual atoms with a predefined maximum displacement, and the resultant geometry is optimized. Using the O PLS-AA force field, two series of oligomers of beta -amino acids with methy l ester terminal groups have been chosen for detailed examination. Monomeri c (S)-3-pyrrolidine-3-carboxylic acid (PCA) and (S)-nipecotic acid (Nip) ha ve 4 and 2 nearly equi-energy conformers, respectively. The dimers and trim ers have substantially larger number of low-energy conformers within 1 kcal /mol of the global minimum. However, the low-energy conformers of the tetra mers can all be classified as belonging to a few distinct families, in term s of variations in total interatomic distances. Even in the absence of hydr ogen bonding, the larger oligomers have two well-defined conformers, a comp act helical form, and an extended structure. The preferences for these form s are determined exclusively by intramolecular dipolar interactions and van der Waals' forces. These results are consistent with experimental CD spect ral trends, which reveal sharp features only for the higher oligomers (n > 3). (C) 2001 John Wiley & Sons, Inc.